The present invention relates to novel substituted cyclohexanols useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. The novel compounds of the present invention are central nervous system agents. More particularly, the novel compounds of the present invention are dopaminergic agents.
A series of 1-(4-arylcyclohexyl)piperidines which may structurally be represented by the formula ##STR1## the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein
Ar.sup.1 is a member selected from the group consisting of aryl and 1,3-benzodioxolyl;
R is a member selected from the group consisting of hydrogen and lower alkyl;
R.sup.1 is a member selected from the group consisting of hydrogen, cyano, carboxyl, lower alkyloxycarbonyl, aryllower alkyloxycarbonyl, aminocarbonyl, mono- and di(lower alkyl)aminocarbonyl, mono- and di(aryllower alkyl)aminocarbonyl, (aryllower alkyl)lower alkylamino carbonyl, hydroxy, lower alkyloxy, lower alkylcarbonyloxy, formyl, lower alkylcarbonyl, arylcarbonyl, aryllower alkylcarbonyl, lower alkyl, lower alkenyl, lower alkynyl and cyclohexyl; and
A is a bivalent radical, having the formula ##STR2## wherein
R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, lower alkyl, and lower alkyloxy; or
A is a bivalent radical, having the formula ##STR3## wherein
Ar.sup.2 is aryl, and
R.sup.4 is a member selected from the group consisting of hydrogen, lower alkyl, aryllower alkyl, cyanolower alkyl, aminolower alkyl, mono- and di(lower alkyl) aminolower alkyl, mono- and di(aryllower alkyl)aminolower alkyl, [(aryllower alkyl)lower alkylamino]lower alkyl, hydroxylower alkyl, mercaptolower alkyl, lower alkyloxylower alkyl, lower alkylthiolower alkyl, aryloxylower alkyl, arylthiolower alkyl, aryllower alkyloxylower alkyl, aryllower alkylthiolower alkyl, and a radical of formula ##STR4## wherein
n is 0 or an integer of from 1 to 6 inclusive, Q is O, S or NR.sup.6, p is 0 or 1, X is O or S, R.sup.5 is hydrogen, lower alkyl, aryl or aryllower alkyl, m is 0 or 1 and Y is O, S or NR.sup.6, wherein R.sup.6 as used in the definition of Q and Y is hydrogen, lower alkyl, aryl or aryllower alkyl;
provided that when Y is O and m and p are each 1, then R.sup.5 is other than hydrogen and provided that when p is 1 then n is other than 0:
wherein aryl is a member selected from the group consisting of phenyl, thienyl, pyridinyl, naphthalenyl and substituted phenyl, said substituted phenyl having from 1 to 3 substituents each independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, phenyl lower alkyloxy, trifluoromethyl, nitro, amino and hydroxy are disclosed in U.S. Pat. No. 4,329,353 as having psychotropic and antiemetic activity.
A series of 4-alkoxy-4-(substituted phenyl)cyclohexylamines of formula ##STR5## where the sign indicates the cis or trans configuration the condition that when the R.sub.3 O bond is cis with respect to the amino group the bond joining the phenyl and cyclohexyl rings is trans and vice versa; R=1-4C alkyl, Cl, F, Br, CF.sub.3, or 1-4C alkoxy; R'=R or H; R.sub.1 =H or 1-4C alkyl; R.sub.2 =H, 1-4C alkyl, aroylalkyl (monosubstituted on the aryl ring by a group R or 6-10C aryl) or bis-arylalkyl (monosubstituted on the ring by a group R' or 6-10C aryl) or R.sub.1 and R.sub.2 together with the N atom form a saturated heterocyclic chosen from pyrrolidino, piperidino, hexamethyleneimino, morpholino, and piperazino (optionally monosubstituted); R.sub.3 =1-4C alkyl; are disclosed in Belgium Patent No. 790836 as having central nervous system depressant activity.
However, the 1-(4-arylcyclohexyl)piperidines disclosed in U.S. Pat. No. 4,329,353 and the 4-alkoxy-4-(substituted phenyl)-cyclohexylamines disclosed in Belgium Patent 790836 do not disclose or suggest the combination of structural variations of the compounds of the present invention described hereinafter.